p-Coumaric Acid and Ursolic Acid fromCorni fructusAttenuated β-Amyloid_25–35-Induced Toxicity through Regulation of the NF-κB Signaling Pathway in PC12 Cells

Abstract

Neuroinflammatory responses induced by amyloid-beta peptide (Aβ) are important causes in the pathogenesis of Alzheimer's disease (AD). Blockade of Aβ has emerged as a possible therapeutic approach to control the onset of AD. This study investigated the neuroprotective effects and molecular mechanisms of p-coumaric acid (p-CA) and ursolic acid (UA) from Corni fructus against Aβ(25-35)-induced toxicity in PC12 cells. p-CA and UA significantly inhibited the expression of iNOS and COX-2 in Aβ(25-35)-injured PC12 cells. Blockade of nuclear translocation of the p65 subunit of nuclear factor κB (NF-κB) and phosphorylation of IκB-α was also observed after p-CA and UA treatment. For the upstream kinases, UA exclusively reduced ERK1/2, p-38, and JNK phosphorylation, but p-CA suppressed ERK1/2 and JNK phosphorylation. Both compounds comprehensively inhibited NF-κB activity, but possibly with different upstream pathways. The results provide new insight into the pharmacological modes of p-CA and UA and their potential therapeutic application to AD.

Anti-inflammatory, antioxidant and anti-acetylcholinesterase activities of Bouvardia ternifolia: potential implications in Alzheimer’s disease

“…Likewise, the triterpenes and ursolic and oleanolic acids (mainly concentrated in fraction BtPPF2) showed potent anti-inflammatory activity in the present study that is consistent with the literature (Liu 1995). Some reports indicate that ursolic acid also reduces Ab-induced oxidative damage, such as free radical formation and lipid peroxidation, in in vitro assay systems, in turn also reducing the production of proinflammatory cytokines, leading to a neuroprotective effect against Ab (Yoo and Park 2012;Yoon et al 2014). Therefore, taking all of this information together, there is the possibility that the neuroprotector properties exerted by BtHA may be due to the anti-inflammatory, the antioxidant and the inhibitory on acetylcholinesterase effects that could be attributed to its contents of polyphenols, coumarins, and triterpenes.…”

Pelargonidin improves memory deficit in amyloid β25-35 rat model of Alzheimer’s disease by inhibition of glial activation, cholinesterase, and oxidative stress

“…Neuroinflammatory responses induced by Ab and overexpression of some proinflammatory molecules like inducible nitric oxide synthase (iNOS) are important in the pathogenesis of AD [38]. Increased GFAP immunoreactivity and reactive astrogliosis have been reported following Ab that resembles the phenotypes in AD patients and in transgenic mouse models of AD 1-40 [39][40][41].…”

Ursolic acid attenuates beta-amyloid-induced memory impairment in mice

“…UA (3β-hydroxy-urs-12-en-28-oic acid) is a lipophilic, pentacyclic triterpenoid compound. UA has a significant anti-oxidant and -inflammatory effect both in vivo and in vitro 17,18 . UA also exerts a neuroprotective effect against D-galactose-induced cognition deficits in mice via the reduction of its anti-oxidant properties 19 .…”

“…UA also exerts a neuroprotective effect against D-galactose-induced cognition deficits in mice via the reduction of its anti-oxidant properties 19 . Moreover, UA suppresses NF-κB signaling, thus attenuating the inflammatory responses of PC12 cells 18 . With this background, the aim of the present study was to evaluate whether UA has a protective effect against cognitive impairment induced by Aβ [25][26][27][28][29][30][31][32][33][34][35] -injected in mice.…”